The Risk of Metastatic Recurrence after Non-Curative Endoscopic Resection with Negative Deep Margins for Early Colorectal Cancer: Two-Center Retrospective Cohort Study.

Introduction: Non-curative endoscopic resection of T1 colorectal cancer (CRC) carries a substantial risk of recurrence. However, previous studies have reported a significant proportion of cases in which the deep margin of endoscopic resection was positive for cancer due to the technical difficulties of colorectal endoscopic submucosal dissection (ESD). With the advancement of endoscopic technology and techniques resulting in the reduction of positive resection margins, it is important to reassess the long-term prognosis and major risk factors for recurrence in cases of negative deep margins.

Methods: We conducted a retrospective cohort study of consecutive patients with T1 CRC who underwent endoscopic resection between January 2006 and December 2021 with negative deep margins. The histological findings of the resected specimens were analyzed to determine the risk factors associated with the primary outcomes of this study, including recurrence and cancer-related deaths.

Results: The median age of the 190 patients was 70 years, of which 63% were male, and endoscopic treatment was performed in 64% by endoscopic mucosal resection and 36% by ESD. Eighty-two patients were in the curative resection (CR) group and 108 were in the non-curative resection (NCR) group, wherein the latter comprised 79 patients who underwent additional surgery (AS) and 29 patients who did not receive AS. Five-year recurrence-free survival rates were 98.4% (95% CI: 89.3-99.8) for CR, 98.3% (95% CI: 88.8-99.8) for NCR with AS, and 73.7% (95% CI: 46.5-88.5) for NCR without AS. Lymphatic invasion and budding grade 2/3 were the major risk factors for recurrence, with hazard ratios of 40.7 (p < 0.001) and 23.1 (p = 0.007), respectively. Of the patients in the NCR group without AS, the 5-year recurrence-free rate was 85.6% (95% CI: 52.5-96.3) if there were no major risk factors (i.e., no lymphatic invasion or budding grade 2/3) (n = 21), whereas the prognosis was poor in the presence of one or more of the major risk factors, with a median recurrence-free survival and disease-specific survival of 2.5 and 3.1 years, respectively (n = 8).

Discussion: In endoscopically resected T1 CRC with negative deep margins, lymphatic invasion or budding grade 2/3 may indicate a higher risk of recurrence when followed up without AS.